Hyperkeratosis and

Lawrence et al. [66] in a split face study, compared the efficacy and safety of Jessner s solution and 35% TCA with 5% fluorouracil in the treatment of widespread facial actinic keratoses. Fifteen patients were treated. Both treatments reduced the number of visible actinic keratoses by 75%. Similarly, both caused equivalent reductions in keratinocyte atypia, hyperkeratosis, and parakeratosis. Compared to fluorouracil, only one application of the peel was necessary. 

A number of skin diseases, mainly characterized by blistering, have been found to be due to mutations in genes encoding various keratins. Three of these disorders are epidermolysis bullosa simplex, epidermolytic hyperkeratosis, and epidermolytic pahnoplantar kerato-derma. The blistering probably reflects a diminished capacity of various layers of the skin to resist mechanical stresses due to abnormalities in microfilament strucmre. 

Chronic ingestion of trivalent arsenic in medicinal preparations was also associated with an increased incidence of hyperkeratosis and... 

In mice exposure to 9 ppm caused a 50% decrease in respiratory rate. Lesions included ulceration and necrosis of the respiratory epithelium and moderate damage to lung tissue. Rats administered, via oral gavage, 10, 20, 40, or 80mg/kg for 10 consecutive days or 32 mg/kg for 90 consecutive days had inflammation, necrosis, acantholysis, hyperkeratosis, and epithelial hyperplasia of the forestomach. Chloropicrin was genotoxic in bacterial test systems."... 

In a follow-up study in mice, exposure to DEA, via drinking water or by topical application, caused dose-dependent toxic effects in the liver (hepatocellular cytological alterations and necrosis), kidney (nephropathy and tubular epithelial necrosis in males), heart (cardiac myoqn e degeneration), and skin (site of application ulceration, inflammation, hyperkeratosis, and acanthosis). Doses ranged from 630 to 10,000 ppm in the drinking water and from 80 to 12 50 mg/kg in the topical application study. 

In a lifetime study, 25-pi aliquots of a 5% solution applied three times a week to the skin of male mice caused a low incidence of dermatitis, hyperkeratosis, and necrosis. There... 

No skin tumors were observed in another strain of mice receiving up to 85% EHA in acetone for up to 2 years. Hyperkeratosis and hyperplasia occurred in all treated groups."... 

No significant effects on reproductive function or pregnancy outcome were found in two-generation reproduction smdies in rats at doses that were toxic, causing hyperkeratosis and benign neoplasms of the forestomach. ... 

Male Fischer 344 rats dosed by gavage with 29 mg/kg bw 1,2-dibromo-3-chloropropane on five days per week for two weeks developed hyperkeratosis and hyperplasia of... 

Signs of methyl bromide toxicity following acute exposure include irritation of the eyes and respiratory tract, tremor, incoordination, depression of the central nervous system and convulsions. Long-term exposure induces pulmonary congestion, central nervous system effects, and renal and hepatic lesions. After oral administration to rats, hyperplasia and hyperkeratosis (and squamous-cell carcinomas) of the forestomach were observed (lARC, 1986). 

Application of diglycidyl resorcinol ether caused irritation to the eyes and skin of rabbits. Once-monthly intravenous injection of the compound at doses of 100-200 mg/kg bw produced a progressive lowering of the leukocyte count in monkeys. Hyperkeratosis and basal-cell hyperplasia in the forestomach were observed in rats and mice exposed daily to intragastric doses of 12.5 mg/kg bw and higher for 13 weeks. In a two-year study in rats, dose-related bronchopneumonia occurred, which was not consistent with chemical pneumonitis, but was characterized by polymorphonuclear leukocytes in the alveoli. The compound also inhibited the growth of Walker carcinoma in rats (lARC, 1985). The occurrence of forestomach hyperkeratosis and epithelial cell proliferation was confirmed in a two-week study in rats with doses of 25 mg/kg bw, but not with 12 mg/kg bw (Ghanayem et al., 1986). 

In general, the levels of arsenic in air and water are low, and the major source of human exposure is food. In certain parts of Taiwan and South America, however, the water contains high levels of this metalloid, and the inhabitants often suffer from dermal hyperkeratosis and hyperpigmentation. Higher levels of exposure result in a more serious condition gangrene of the lower extremities or blackfoot disease. Cancer of the skin also occurs in these areas. 

Signs and symptoms of mild vitamin A deficiency are easily overlooked. Skin lesions, such as follicular hyperkeratosis and infections, are among the earliest signs of deficiency, but the most... 

Dermal Effects. Dermal effects of several CDD congeners have been studied in animals. Acute dermal exposure to 0.01 g (newborn) and 0.1 g 2,3,7,8-TCDD (adult) per animal caused hyperkeratosis and epidermal hyperplasia in hairless HRS/J mice (Puhvel and Sakamoto 1988). An involution of sebaceous glands was found in both (haired and hairless) strains. Similar results were found following intermediate-duration exposure (Puhvel et al. 1982). Furthermore, acne-like lesions in the ears were found in CD-I mice following exposure to 0.1 g 2,3,7,8-TCDD applied on the pre-shaved back 2 days a week for 30 weeks (Berry et al. 1978, 1979). In contrast, no dermal effects were observed in Swiss Webster mice exposed to 0.005 g 2,3,7,8-TCDD/application, 3 days a week for up to 104 weeks (NTP 1982a). 

The two most severe types of ichthyosis, lamellar ichthyosis (LI) and epidermolytic hyperkeratosis (EHK), are distinct families of diseases with completely different etiologies (see Figure 8.1 and Table 8.3). Nevertheless, LI and EHK have several things in common they are rare, congenital diseases (prevalence <1/100,000) with more or less generalized hyperkeratosis and a defective skin barrier, and they usually demands vigorous therapy. 

Virtanen, M., Gedde-Dahl, T., Mork, N.-J., Leigh, I., Bowden, P.E., and Vahlquist, A., Phenotypic/ genotypic correlations in patients with epidermolytic hyperkeratosis and the effects of retinoid therapy on keratin expression, Acta Derm. Venereol., 81, 163-170, 2001. 

The epidermis plays a role in skin mechanics. Thereby, hydrophilic as well as hydrophobic substances affect mechanical properties of the skin. Changes in skin mechanics can be the result of either a direct influence of a substance on the intercellular matrix, or an epiphenomenona, for example, a physiological shift of water between the tissues aimed to maintain physiological homeostasis, 50 The hydration level of the SC affects its mechanical properties. Increased hydration of the SC influences its extensibility and elasticity.51-54 Examples from human diseases such as ichthyotic and xerotic disorders indicate that thickening of the SC due to hyperkeratosis and increased corneocyte cohesion is responsible for a marked decrease in the flexibility of the entire SC.55... 

Low levels of LA are found in the sebum of acne sufferers,200 and levels appear inversely related to sebum secretion rate.201 It has been hypothesized that this local EFA deficiency may lead to the follicular hyperkeratosis and occlusion of acne, and that an increased supply of linoleate might possibly ameliorate the condition.202 In support of this, digital image analysis revealed that topical application of LA over a one month period reduced the size of microcomedones.203 Decreased levels of LA may also contribute to acne inflammation by failing to inhibit phagocytosis and ROS generation by neutrophils.204... 

No histopathological lesions were observed in esophageal and stomach tissue or in the small intestine and colon from male and female Fischer 344 rats or B6C3Fj mice given oral doses of 0,25, 50, 100, 200, 400, or 600 mg/kg/day benzene in com oil for 120 days (NTP 1986). After chronic-duration exposure to 50-200 mg/kg/day (male rats) or 25-100 mg/kg/day (female rats, male and female mice), male rats exhibited hyperkeratosis and acanthosis in the nonglandualar forestomach at 200 mg/kg/day, and mice exhibited epithelial hyperplasia and hyperkeratosis in the forestomach at >25 mg/kg/day (NTP 1986). 

In chronic arsenic poisoning anorexia, anaemia, disturbances in renal and hepatic function, dermatitis, skin hardening (hyperkeratosis) and pigmentation can occur. Arsine gas is a powerful haemolytic agent and symptoms of poisoning are due to its action on the blood. 

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